The clinical features of fungal meningitis similar to any other cause of meningitis. It can present with fever, neck stiffness, nausea, photophobia, vomiting, headache and mental status changes [5] [6]. Fungal meningitis is non-contagious as compared to bacterial and viral meningitis that are known to be contagious. Fungal meningitis can occur only due to hematogenous or contiguous spread from a local site of infection to the CNS [5] [6]. It is typically found in immunocompromised hosts, although the causitive pathogen can vary according to the local environment [6] [7].

Clinical features of fungal meningitis are indistinguishable from other causes of meningitis and hence require various laboratory tests to obtain a diagnosis. The presenting signs and symptoms may consist of the following:

• Photophobia
• Nausea and vomiting
• Myalgia
• Arthralgia
• Problems with coordination 
• Drowsiness/Confusion
• Headache
• Convulsions
• Altered mental status
• Fever 
• Neck stiffness
• Dizziness
• Amnesia

• Fever

  School Exclusion Criteria Children with fungal meningitis should be kept out of school or childcare until they are fever free for 24 hours without the use of fever suppressing medications. [dshs.state.tx.us]

  pyorrhea, pyorrhea alveolaris, rabbit fever, rabies, rat-bite fever, reactive inflammation, relapsing fever, rheumatic fever, rheumatism, rheumatiz, rheumatoid arthritis, rhinitis, rickettsialpox, ringworm, rubella, rubeola, scarlatina, scarlet fever [mereja.com]

  You have a headache, fever, and stiff neck. You are confused. When should I contact my healthcare provider? You have a fever. You have questions or concerns about your condition or care. Care Agreement You have the right to help plan your care. [drugs.com]

  Valley Fever and Pregnant Women. State of California Health and Human Services Agency. January 2016. Valley Fever Statistics. CDC. November 9, 2017. Thomas M. The Mysterious Fungus Infecting the American Southwest. The Atlantic. August 8, 2014. [everydayhealth.com]

• Inflammation

  enteritis, equine encephalomyelitis, erysipelas, exudative inflammation, famine fever, fibroid inflammation, five-day fever, flu, focal inflammation, frambesia, gastritis, gingivitis, glandular fever, glossitis, gonococcal arthritis, gonorrheal arthritis [mereja.com]

  A slight degree of inflammation and low-grade fever were recorded. A tentative diagnosis of fungal meningitis was made and anti-fungal therapy was administered transventricularly and transvenously. [ncbi.nlm.nih.gov]

  Meningitis results in inflammation of the membranes covering the brain and spinal cord. The problems came to light in fall 2012, after the first cases were reported. [britmycolsoc.org.uk]

• Fatigue

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019 [patientslikeme.com]

  Two weeks later, at a home visit conducted by the Virginia health department, his only symptom was fatigue. " Exserohilum meningitis is a new clinical entity," Smith and colleagues noted, so "it is not known whether the current treatment guidance is sufficient [medpagetoday.com]

  At a home visit conducted by the health department 2 weeks later, the patient reported only fatigue. [nejm.org]

  She’d been treated for neck pain and a chronic condition called fibromyalgia that is defined by aches and pains all over the body and general weakness and fatigue. [vitals.nbcnews.com]

• Candidiasis

  Cryptococcal meningitis and candidiasis patients accrued the largest average charges ($103 236 and $103 803, respectively) and spent the most time in the hospital on average (70.6 and 79 days). [ncbi.nlm.nih.gov]

  Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. [scienceopen.com]

  Candidiasis is usually acquired in an inpatient setting. The route of transmission for most fungal infections is usually thorough inhalation of spores. Meningitis occurs when the fungal infection spreads to the brain. [symptoma.com]

  Yeast Infections Yeast infections of the skin are called cutaneous candidiasis and are caused by yeast-like fungi called candida. They occur when yeast on the skin grows more actively and causes a red, scaling, itchy rash on the skin. [m.webmd.com]

  Guidelines for Treatment of Candidiasis. Clinical Infectious Diseases. January 15, 2004. Perfect JR, Dismukes WE, Dromer F, et al. [everydayhealth.com]

• Malaise

  Clinical features May be associated with features of pneumonia More appropriately termed meningoencephalitis as brain parenchyma is also involved Onset over several weeks: headache fever malaise altered mental status Clinical signs often absent but may [aic.cuhk.edu.hk]

• Cough

  They easily spread through coughing and sneezing. Direct or indirect contact with an infected person increases your risk of getting the same virus. [healthline.com]

  Meningitis is contagious and may spread through coughing, sneezing, and any sort of close contact. [healthhype.com]

  Prevention Some forms of bacterial meningitis are contagious and usually spread through respiratory and throat secretions (oral contact and exposure to coughing or sneezing). [sheknows.com]

  The bacteria that cause meningitis can spread when people who are infected cough or sneeze. If you or your child has been around someone who has bacterial meningitis, ask your doctor what steps you should take to avoid catching it. [webmd.com]

• Sneezing

  They easily spread through coughing and sneezing. Direct or indirect contact with an infected person increases your risk of getting the same virus. [healthline.com]

  Meningitis is contagious and may spread through coughing, sneezing, and any sort of close contact. [healthhype.com]

  Prevention Some forms of bacterial meningitis are contagious and usually spread through respiratory and throat secretions (oral contact and exposure to coughing or sneezing). [sheknows.com]

  The bacteria that cause meningitis can spread when people who are infected cough or sneeze. If you or your child has been around someone who has bacterial meningitis, ask your doctor what steps you should take to avoid catching it. [webmd.com]

• Nausea

  Early symptoms of fungal meningitis, such as headache, fever, dizziness, nausea and slurred speech, are subtler than those of bacterial meningitis and can take nearly a month to appear. [abcnews.go.com]

  These include headache, nausea, vomiting, stiffness of the neck, fever and inability to tolerate bright light. [symptoma.com]

  Symptoms include: fever headache stiff neck nausea and vomiting sensitivity to light A recent outbreak of fungal meningitis has been reported in numerous states by patients who have received contaminated steroid injections. [atlanticapothecary.com]

  Symptoms can include a fever, headache, nausea and vomiting. However, if you suspect meningitis you can have samples of your blood or cerebro-spinal fluid tested. [radiomd.com]

• Vomiting

  These include headache, nausea, vomiting, stiffness of the neck, fever and inability to tolerate bright light. [symptoma.com]

  Symptoms include: fever headache stiff neck nausea and vomiting sensitivity to light A recent outbreak of fungal meningitis has been reported in numerous states by patients who have received contaminated steroid injections. [atlanticapothecary.com]

  […] condition such as aids, cancer, diabetes usually takes longer to cure. https://microbewiki.kenyon.edu/images/thumb/6/6a/Hivcryptoneo.jpg/300px-Hivcryptoneo.jpg https://healthinessbox.files.wordpress.com/2012/10/fig33.jpg Symptoms Headache Stiff neck Fever Vomiting [sites.google.com]

  Symptoms can include a fever, headache, nausea and vomiting. However, if you suspect meningitis you can have samples of your blood or cerebro-spinal fluid tested. [radiomd.com]

  Symptoms may include: Fever Hallucinations Headache Mental status change (confusion) Nausea and vomiting Sensitivity to light Stiff neck Your health care provider will examine you. [medlineplus.gov]

• Eye Pain

  A severe headache, stiff neck, and a fever Neck pain Nausea or vomiting Eye pain when you look into bright lights Sleepiness or confusion How is fungal meningitis diagnosed? Your healthcare provider will examine you and ask about your symptoms. [drugs.com]

• Flushing

  “I was very scared in the beginning,” Hall said last week, just before going into surgery to flush out the infected joint. “Now it’s to the point. .. I want it over with so I can start healing and feeling better.” [bostonglobe.com]

• Back Pain

  The outbreak has been linked to spinal steroid injections, a common treatment for back pain. [abcnews.go.com]

  An autopsy was performed when it was noted that the patient had received an epidural steroid injection 2 weeks earlier to treat low-back pain. [mdedge.com]

  Health officials in the United States are attempting to contact patients who recently received steroid injections for back pain. That is because the injections may have been carrying a fungus. [learningenglish.voanews.com]

  All 3 patients presented with acute ischemic strokes and had a history of epidural spinal injections of methylprednisolone for low back pain. All 3 patients had 1 or more traditional risk factors for stroke. [ncbi.nlm.nih.gov]

• Low Back Pain

  An autopsy was performed when it was noted that the patient had received an epidural steroid injection 2 weeks earlier to treat low-back pain. [mdedge.com]

  All 3 patients presented with acute ischemic strokes and had a history of epidural spinal injections of methylprednisolone for low back pain. All 3 patients had 1 or more traditional risk factors for stroke. [ncbi.nlm.nih.gov]

  The injections were primarily given as epidural injections to older adults with low back pain and possibly as intra-articular injections. [annals.org]

  In 2012, fungal meningitis was linked to a contamination in a specific steroid product, methylprednisolone, manufactured in a single pharmacy and injected in the spine of people suffering from low back pain. [emedicinehealth.com]

• Hearing Impairment

  Possible after-effects/resulting disabilities: Physical/specific hearing impairments/deafness/tinnitus loss of sight/changes in eyesight (not necessarily permanent) brain damage (severe damage only occurs in 2% of cases) stiffness in joints loss of balance [deafblind.com]

• Meningism

  Meningitis victim suing pharmacy Separate lawsuits seeking a total of $15 million have been filed in Virginia against a Massachusetts pharmacy that is at the center of an outbreak of rare fungal meningitis. [boston.com]

  Using the manufacturer's cutoff value (≥80 pg/ml), the sensitivity and specificity were 96% and 95%, respectively, for proven meningitis and 84% and 95% for probable or proven meningitis. [ncbi.nlm.nih.gov]

  CNN) More than 700 people in 20 states were diagnosed with fungal meningitis and other infections after receiving contaminated medication in 2012. Sixty-four patients in nine states died, making it the deadliest meningitis outbreak in US history. [britmycolsoc.org.uk]

• Headache

  A week later, she developed the severe headache – so bad it drove her to the ER. Now, of course, doctors know that anyone who has had a steroid injection and shows up with symptoms like a severe headache should be checked for infection. [vitals.nbcnews.com]

  Early symptoms of fungal meningitis, such as headache, fever, dizziness, nausea and slurred speech, are subtler than those of bacterial meningitis and can take nearly a month to appear. [abcnews.go.com]

• Confusion

  You are confused. When should I contact my healthcare provider? You have a fever. You have questions or concerns about your condition or care. Care Agreement You have the right to help plan your care. [drugs.com]

  Symptoms of meningitis include headache, fever, stiff neck, dizziness, confusion, and even strokes, as well as swelling, redness or discharge from the site of the injection. Get treatment right away for those symptoms. [thefloridafirm.com]

  Symptoms of fungal meningitis are generally similar to those of other types of meningitis, and include: a fever, stiff neck, severe headache, photophobia (sensitivity to light), nausea and vomiting, and altered mental status (drowsiness or confusion). [en.wikipedia.org]

  Also those with fungal meningitis may also experience, dislike of bright lights, changes in mental status, confusion, hallucinations, and personality changes Those at high risk for fungal meningitis include those who have certain medical conditions like [dshs.state.tx.us]

• Neck Stiffness

  Signs and Symptoms of Fungal Meningitis Elevated body temperature Headaches Neck stiffness Nausea Vomiting Light sensitivity Mental status alteration Diagnosis for Fungal Meningitis If there is a suspicion of meningitis blood draws are taken and also [epainassist.com]

  “Fever, new or worsening headache, sometimes neck stiffness. We’ve also seen in a few patients signs and symptoms of stroke, sudden onset of slurred speech, dizziness, difficulty walking, sudden weakness.” [learningenglish.voanews.com]

  These include headache, nausea, vomiting, stiffness of the neck, fever and inability to tolerate bright light. [symptoma.com]

  Like other forms of meningitis, typical symptoms associated with fungal meningitis include fever and headache, neck stiffness/pain and deterioration of mental status (drowsiness, stupor and coma). Cranial nerve deficits and seizures can also occur. [nervous-system-diseases.com]

• Altered Mental Status

  Symptoms of fungal meningitis are generally similar to those of other types of meningitis, and include: a fever, stiff neck, severe headache, photophobia (sensitivity to light), nausea and vomiting, and altered mental status (drowsiness or confusion). [en.wikipedia.org]

  Clinical features May be associated with features of pneumonia More appropriately termed meningoencephalitis as brain parenchyma is also involved Onset over several weeks: headache fever malaise altered mental status Clinical signs often absent but may [aic.cuhk.edu.hk]

  Top of Page Signs and Symptoms Signs and symptoms of fungal meningitis may include the following: Fever Headache Stiff neck Nausea and vomiting Photophobia (sensitivity to light) Altered mental status (confusion) Diagnosis If meningitis is suspected, [cdc.gov]

  A: “Signs and symptoms of fungal meningitis are similar to those of meningitis from other causes and may include the following: headache, fever, sensitivity to light, stiff neck, nausea and vomiting, and altered mental status. [daytondailynews.com]

For any case with suspected meningitis, blood and cerebrospinal fluid (CSF) samples are sent for laboratory evaluation urgently, since the treatment varies according to the causitive agent. The tests include:

• Lumbar puncture (LP) and CSF analysis

In fungal meningitis, an elevated opening pressure of CSF during LP has been associated with poor prognosis.

• CSF findings for fungal meningitis

CSF analysis usually exhibit decreased glucose levels, high protein levels and a lymphocytic pleocytosis in the range of 10-200 cells/µl for most fungal causes of meningitis, including Cryptococcosis. Rarely, cases of C. immitis have been associated with eosinophilic pleocytosis.

• CSF culture, blood culture

These can be used as a mode of obtaining a definitive diagnosis for certain fungal pathogens, such as H. capsulatum, B. dermatitidis, C. immitis and Candida spp.

• Fungal serology

The detection fungal antigens is frequently used for diagnosing fungal meningitis, especially for histoplasmosis. Serology is helpful for diagnosing the fungi that are difficult to culture. However, in certain cases such as B. dermatitidis, serology is not considered conclusive since a negative test fails to rule out the diagnosis.

The treatment for fungal meningitis usually consists of high-dose anti-fungal medications administered intravenously (IV) in an inpatient setting. The treatment duration is variable, and depends upon factors such as the immune status of the patient and the pathogen involved [5] [6]. Patients diagnosed with comorbidities such as diabetes, cancer and AIDS that compromise the immune system usually have a prolonged course of treatment [5] [6].

Cryptococcal meningitis

It is known to be an opportunistic infection in individuals diagnosed with HIV/AIDS. Treatment consists of amphotericin B (0.7-1 mg/kg/day IV) for a minimum of 2 weeks. Flucytosine (100mg/kg by mouth in 4 divided doses) can also be added. Liposomal amphotericin B (amphotericin B liposome 3-4 mg/kg/day or amphotericin B lipid complex 5 mg/kg/day) may be considered in cases with predisposition to or pre-existing renal dysfunction. The consolidation phase of the therapy involves administering fluconazole (400 mg/day) for 8 weeks. Itraconazole can be used as an alternative if the patient is not able to tolerate fluconazole. The maintenance phase of the therapy consists of fluconazole 200 mg/day to prevent relapse. Fluconazole is known to be superior to itraconazole and amphoterecin B (1 mg/kg once a week), both, for preventkion of relapse. Cases with HIV/AIDS have a higher risk of relapse.

In places with limited resources, fluconazole and amphotericin B are considered as optimal for treating HIV/AIDS associated acute cryptococcal meningitis. It is recommended that the administration linked to healthcare services in countries with inadequate health facilities should consider providing drugs such as flucytosine that are often unavailable at these places, to optimize HIV treatment programs [8].

Coccidioides immitis

C. immitis associated meningitis is treated with fluconazole (400 mg/day by mouth). Some practitioners prefer initiating the treatment with a higher dose of fluconazole (up to a maximum of 1000 mg/day) or intrathecal amphotericin B and fluconazole combination. The efficacy of itraconazole (400-600 mg/day) is comparable to the aforementioned options. Miconazole IV may also be considered. C. immitis meningitis often requires lifelong treatment.

Histoplasma capsulatum

The preferred option for treating meningitis secondary to H. capsulatum is liposomal amphotericin B, dosage being 5 mg/kg/day IV, with a total of 175 mg/kg over 4-6 weeks). This is followed by a minimum 1 year therapy with itraconazole (200-300 mg BID to TID) till the abnormalities in CSF are resolved and/or histoplasma antigen levels return to normal reference range. The level of itraconazole in blood must be monitored periodically to ensure adequate absorption of the drug. 

Candida species

The drug of choice for the treatment of meningitis due to Candida is amphotericin B (0.7 mg/kg/day). Another drug, flucytosine (25 mg/kg QID, dosage adjusted to obtain serum level of 40-60 µg/ml) is often added to amphotericin B. Suppresive or follow-up therapy usually involves using azoles.

There is a high risk of relapse in candidal meningitis. Treatment is usually continued for four weeks after resolution of symptoms, however, there are no specific guidelines for the duration of the treatment. If candidal meningitis has occured secondary to neurosurgical procedures, removal of any implanted prosthetic materials, such as ventriculoperitoneal shunts, that are suspected of being a nidus for infection should be considered.

Sporothrix schenckii

The best initial therapy is liposomal amphotericin B, and itraconazole (200 mg BID) as a step-down once the patient responds to amphotericin B. The total duration of therapy should be a minimum of 12 months. Itraconazole can also be used as lifelong suppression therapy, but only after initial therapy with amphotericin B. Itraconazole is more effective against S. schenckii that fluconazole.

Exserohilum rostratum

According to the current guidelines from CDC, liposomal amphotericin B or voriconazole IV are the most optimal options for treating E. rostratum [9].

Fungal meningitis has been associated with frequent treatment related complications, neurological sequelae and a high rate of mortality [4]. It often requires close monitoring and counselling for treatment adherence due to high rates of relapse associated with early termination of treatment.

The most frequently encountered pathogen that causes fungal meningitis is Cryptococcus neoformans. It commonly inhabits the soil and is widely found in the environment. Infection occurs through inhalation of air-borne spores. Interestingly, the inhalation of spores does not result in an infection in healthy hosts, rather only those individuals who are immunocompromised, as they are unable to prevent the survival and growth of the fungal spores [1]. C. neoformans infection can present as cutaneous lesions, pulmonary involvement and central nervous system (CNS) disease, including meningitis [2].

C. neoformans is frequent fungal cause of meningitis in immunocompromised hosts. In Africa, it is one of the more common causes of meningitis in adults. Likewise, certain fungal pathogens are endemic to specific parts of United States. For instance, Histoplasma capsulatum is found individuals with a history of contact with bat and bird droppings, typically in Midwestern part of United States. On the other hand, Coccidioides infection, also known as valley fever, is more prevalent in the Southwest region and usually is found in Filipinos, African Americans, immunocompromised hosts and women in third trimester of pregnancy.

The blood-brain barrier formed by meninges protects the brain from the components of immune system in the blood. In situations where the blood-brain barrier is disrupted, such as meningitis, pathogens can disseminate to the brain and may spread rapidly due to partial isolation from the immune system. As the body develops an immune response to the infection, there is inflow of fluid, white blood cells (WBCs) and other inflammatory mediators due to the increased permeability of blood vessels in the meninges and brain. This may lead to cerebral edema that will lead to symptomatic worsening of the patient due to diminished blood flow to various parts of the brain [3].

Fungal meningitis is a non-contagious disease. It may occur due to hematogenous dissemination or by contiguous spread from a local infection. Medications such as steroids, anti-TNF (tumor necrosis factor) agents and those prescribed status-post organ transplantation, are known to weaken the immune system and lead to an increased risk for developing fungal meningitis.

Cryptococcosis occurs due to inhalation of soil that is contaminated with bird droppings. Histoplasma is prevalent in places like caves with bat and bird droppings, typically in the Ohio and Mississippi river valleys. Blastomyces is commonly found in soil that has decaying organic matter, and is mostly prevalent in the northern Midwest region of United States. Coccidioides is endemic to Southwest United States, along with certain parts of South and Central Americas. Candidiasis is usually acquired in an inpatient setting. The route of transmission for most fungal infections is usually thorough inhalation of spores. Meningitis occurs when the fungal infection spreads to the brain.

Avoidance of the specific environments that are most likely to have fungal spores is the best way to prevent infection. Immunocompromised individuals should be advised to avoid dusty environments, digging activities and bird droppings, especially if they dwell in a region with prevalence of Histoplasma, Blastomyces or Coccidioides.

Meningitis is defined as a clinical syndrome that involves inflammation of the meninges. Fungal meningitis occurs usually due to dissemination of a hematogenous fungal infection to the spinal cord. It is a rare cause of meningitis and frequently occurs in immunocompromised states such as cancer and HIV infection. 

Fungal meningitis is a rare disease. It occurs due to spread of a fungus from the blood to the brain and spinal cord. The clinical signs and symptoms that you may experience are similar to those from meningitis due to any other cause. These include headache, nausea, vomiting, stiffness of the neck, fever and inability to tolerate bright light. Unlike several other forms of meningitis, fungal meningitis is a non-contagious disease and occurs only if the infection enters the blood or gains direct access to the brain and spinal cord from a nidus close to these organs. The treatment for fungal meningitis involves the use of high dose anti-fungal drugs, that are given intravenously for several months. The duration of receiving the treatment, however, varies depending on how good your immune system is working and the type of fungus causing your condition.

1. Meningitis Research Foundation. (2003). About the diseases - Fungal Last accessed, Meningitis Research Foundation. 20/3/03. www.meningitis.org/sect5/subsect10.
2. Cryptococcosis, Mycology Online. Cryptococcosis, University of Adelaide Australia. 2003.
3. Berkhout B. Infectious diseases of the nervous system: pathogenesis and worldwide impact. IDrugs. 2008 Nov. 11(11):791-5.
4. Greenberg DA, Aminoff MJ, Simon RP. Chapter 4. Confusional States. In: Greenberg DA, Aminoff MJ, Simon RP, eds. Clinical Neurology. 8th ed. New York: McGraw-Hill; 2012.
5. Fungal Meningitis. Centers for Disease Control and Prevention. 2012. Available at: http://www.cdc.gov/meningitis/fungal.html. 
6. Roos KL, Tyler KL. Chapter 381. Meningitis, Encephalitis, Brain Abscess, and Empyema. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
7. Koroshetz WJ. Chapter 382. Chronic and Recurrent Meningitis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
8. Sloan D, Dlamini S, Paul N, Dedicoat M. Treatment of acute cryptococcal meningitis in HIV infected adults, with an emphasis on resource-limited settings. Cochrane Database Syst Rev. 2008 Oct 8. CD005647.
9. Multistate Fungal Meningitis Outbreak Investigation. Centers for Disease Control and Prevention. 2012. Available at: http://www.cdc.gov/hai/outbreaks/meningitis.html.